Integrative single-cell profiling of melanoma reveals a tumor microenvironment signature predictive of immunotherapy response

Background: Immune checkpoint inhibitors have transformed cancer treatment, yet a large number of patients fail to respond. Identifying molecular characteristics that predict response before treatment initiation remains an unmet need. Towards that end, this study presents a large-scale integrative analysis of existing single-cell and bulk tissue datasets, aimed at identifying predictive features while providing insights into their cellular origin and potential function within the tumor microenvironment. Methods: A stepwise analysis was performed using single-cell RNA-sequencing data from 60 melanoma patients at baseline, separated into discovery (n=41) and validation (n=19) sets. An integrat